Ibuprofen, an inhibitor of prostanoid biosynthesis is the most common pharmacological agent used for the management of pain, inflammation and fever. However, the chronic use of ibuprofen at high doses is associated with increased risk for cardiovascular, renal, gastrointestinal and liver injuries. The underlying mechanisms of ibuprofen-mediated effects on mice liver and proteasome function remain unclear. To determine the mechanisms and pathways affected by ibuprofen treatment (100mg/kg for 7 days), we performed proteomic profiling of male mice liver with quantitative LC-MS/MS using ten-plex tandem mass tag (TMT) labeling. More than 300 proteins were significantly altered between the control and ibuprofen-treated groups. Independent validation of proteomic data by Western blotting was carried out on 14 proteins using both male and female samples. Additional proteasome and immunoproteasome activity/expression was assayed to evaluate differences in proteasome function between male and female mice liver. Our data suggests that these differentially expressed proteins were found to be associated with several major pathways including (1) energy metabolism, (2) protein degradation, (3) fatty acid synthesis and (4) anti-oxidant system. The study suggests that the sex-related differences in the energy metabolism and proteasome dysfunction are underlying mechanisms for ibuprofen-mediated effects in mice liver and provide insights on novel molecular targets for future drug discovery and development.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
|Principal Investigators:||Aldrin V. Gomes, UC Davis, United States|
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